The role of adenosine in rat coronary flow regulation during respiratory and metabolic acidosis

• Published in: European journal of pharmacology 1998-09, Vol.356 (2), p.199-206
• Main Authors: Phillis, John W., Song, Dekun, O'Regan, Michael H.
• Format: Article
• Language: English
• Subjects: Acidosis; Acidosis - physiopathology; Acidosis, Respiratory - physiopathology; Adenosine; Adenosine - physiology; Adenosine receptor; Animals; Biological and medical sciences; Caffeine - pharmacology; Coronary Circulation - drug effects; Coronary Circulation - physiology; Coronary flow; Dipyridamole; Fundamental and applied biological sciences. Psychology; Hemodynamics. Rheology; Hypercapnia; Hypercapnia - drug therapy; Male; Medical sciences; Metabolic diseases; Miscellaneous; Other metabolic disorders; Purinergic P1 Receptor Antagonists; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; SCH 58261; Theophylline - analogs & derivatives; Theophylline - pharmacology; Triazines - pharmacology; Triazoles - pharmacology; Vertebrates: cardiovascular system; ZM 241385
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00512-3

The role of adenosine in rat coronary flow regulation during acidosis was evaluated in isolated, perfused, Langendorff rat heart preparations exposed to brief periods of hypercapnic or metabolic acidosis. Acidosis resulted in increases in coronary flow rate, in conjunction with decreases in ventricular contractile tensions. Heart rates were non-significantly increased. Two non-selective adenosine antagonists, caffeine and 8-phenyltheophylline, markedly attenuated the increases in coronary flow during hypercapnic acidosis without affecting the decline in contractile tension or the heart rate. ZM 241385 (4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3- a]triazin-5-yl amino]ethyl)phenol), a selective adenosine A 2A receptor antagonist, also blocked hypercapnic acidosis-evoked coronary flow rate increases. The adenosine A 1 selective antagonist, 8-cyclopentyl-1,3-dipropylxanthine, did not affect flow rate increases during hypercapnic acidosis. SCH 58261 (5-amino-7-(2-phenyl ethyl)-2-(2-furyl)pyrazolo-[4,3-e]-1,2,4-triazolo[1,5- c] pyrimidine, a selective adenosine A 2A receptor antagonist, blocked the increases in coronary flow rate evoked by metabolic acidosis. An adenosine transport inhibitor, dipyridamole, doubled coronary flow rates during hypercapnic acidosis. When taken in conjunction with previous reports that acidosis enhances adenosine release from cardiac preparations, these results suggest that adenosine is a significant contributor to acidosis-evoked increases in coronary flow.